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Breast cancer immunotherapy

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https://www.readbyqxmd.com/read/28819386/the-tumor-microenvironment-and-inflammatory-breast-cancer
#1
REVIEW
Aji Huang, Shousong Cao, Lili Tang
Inflammatory breast cancer (IBC) is a rare and very aggressive subtype of breast cancer with clinical manifestations similar to acute inflammation. The prognosis of IBC is still poor even though combination therapy with surgery, chemotherapy, and target therapy, mainly due to a lack of fully understanding of the cellular and molecular mechanisms of IBC pathogenesis and progression. In the present article, we have comprehensively reviewed the connection of the pathogenesis of IBC and inflammation, immune reaction and cancer, particularly focused on the role and mechanism of tumor microenvironment related to IBC formation, tumor cell proliferation, migration, invasion and metastasis as well as the clinical manifestations of IBC...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28819027/combination-therapy-with-bispecific-antibodies-and-pd-1-blockade-enhances-the-antitumor-potency-of-t-cells
#2
Chien-Hsing Chang, Yang Wang, Rongxiu Li, Diane L Rossi, Donglin Liu, Edmund A Rossi, Thomas M Cardillo, David M Goldenberg
The DOCK-AND-LOCK (DNL®) method is a platform technology that combines recombinant engineering and site-specific conjugation to create multispecific, multivalent antibodies of defined composition with retained bioactivity. We have applied DNL® to generate a novel class of trivalent bispecific antibodies (bsAbs), each comprising an anti-CD3 scFv covalently conjugated to a stabilized dimer of different anti-tumor Fabs. Here we report the further characterization of two such constructs, (E1)-3s and (14)-3s, which activate T cells and target Trop-2- and CEACAM5-expressing cancer cells, respectively...
August 17, 2017: Cancer Research
https://www.readbyqxmd.com/read/28817603/expression-of-the-mhc-class-ii-in-triple-negative-breast-cancer-is-associated-with-tumor-infiltrating-lymphocytes-and-interferon-signaling
#3
In Ah Park, Seong-Hye Hwang, In Hye Song, Sun-Hee Heo, Young-Ae Kim, Won Seon Bang, Hye Seon Park, Miseon Lee, Gyungyub Gong, Hee Jin Lee
Tumor-infiltrating lymphocytes (TILs) have been known for their strong prognostic and predictive significance in triple-negative breast cancer (TNBC). Several mechanisms for TIL influx in TNBC have been elucidated. Major histocompatibility complex class II (MHC-II) is an essential component of the adaptive immune system and is generally restricted to the surface of antigen-presenting cells. However, it has been reported that interferon-gamma signaling may induce MHC-II in almost all cell types, including those derived from cancer...
2017: PloS One
https://www.readbyqxmd.com/read/28813415/cdk4-6-inhibition-triggers-anti-tumour-immunity
#4
Shom Goel, Molly J DeCristo, April C Watt, Haley BrinJones, Jaclyn Sceneay, Ben B Li, Naveed Khan, Jessalyn M Ubellacker, Shaozhen Xie, Otto Metzger-Filho, Jeremy Hoog, Matthew J Ellis, Cynthia X Ma, Susanne Ramm, Ian E Krop, Eric P Winer, Thomas M Roberts, Hye-Jung Kim, Sandra S McAllister, Jean J Zhao
Cyclin-dependent kinases 4 and 6 (CDK4/6) are fundamental drivers of the cell cycle and are required for the initiation and progression of various malignancies. Pharmacological inhibitors of CDK4/6 have shown significant activity against several solid tumours. Their primary mechanism of action is thought to be the inhibition of phosphorylation of the retinoblastoma tumour suppressor, inducing G1 cell cycle arrest in tumour cells. Here we use mouse models of breast carcinoma and other solid tumours to show that selective CDK4/6 inhibitors not only induce tumour cell cycle arrest, but also promote anti-tumour immunity...
August 16, 2017: Nature
https://www.readbyqxmd.com/read/28804691/combination-of-celecoxib-celebrex-%C3%A2-and-cd19-car-redirected-ctl-immunotherapy-for-the-treatment-of-b-cell-non-hodgkin-s-lymphomas
#5
REVIEW
Tam Nm Dinh, Alexandra S Onea, Ali R Jazirehi
The nonsteroidal anti-inflammatory drug (NSAID) Celecoxib (Celebrex(®)) received Food and Drug Administration (FDA) approval in 1998 for treatment of osteoarthritis and rheumatoid arthritis, and in recent years, its use has been extended to various types of malignancies, such as breast, colon, and urinary cancers. To maintain the survival of malignant B cells, non-Hodgkin's Lymphoma (NHL) is highly dependent on inflammatory microenvironment, and is inhibited by celecoxib. Celecoxib hinders tumor growth interacting with various apoptotic genes, such as cyclooxygenase-2 (Cox-2), B-cell lymphoma 2 (Bcl-2) family, phosphor-inositide-3 kinase/serine-threonine-specific protein kinase (PI3K/Akt), and inhibitors of apoptosis proteins (IAP) family...
2017: American Journal of Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28801472/breast-cancer-immunotherapy-facts-and-hopes
#6
Leisha A Emens
Immunotherapy is revolutionizing the management of multiple solid tumors, and early data have revealed the clinical activity of PD-1/PD-L1 antagonists in small numbers of metastatic breast cancer patients. Clinical activity appears more likely if the tumor is triple negative, PD-L1+, and/or harbors higher levels of TILs. Responses to atezolizumab and pembrolizumab appear to be durable in metastatic triple negative breast cancer (TNBC), suggesting these agents may transform the lives of responding patients. Current clinical efforts are focused on developing immunotherapy combinations that convert non-responders to responders, deepen those responses that do occur, and surmount acquired resistance to immunotherapy...
August 11, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28799073/immunotherapy-in-breast-cancer-the-emerging-role-of-pd-1-and-pd-l1
#7
REVIEW
François Bertucci, Anthony Gonçalves
PURPOSE OF REVIEW: The purpose of the review is to summarize the data regarding PD-L1 expression in breast cancer and the results of first clinical trials with PD-1 or PD-L1 inhibitors in patients with metastatic breast cancer. RECENT FINDINGS: PD-L1 expression is heterogeneous across primary breast cancers, and is generally associated with the presence of tumor-infiltrating lymphocytes and the presence of poor-prognosis features such as high grade, and aggressive molecular subtypes (triple-negative (TN), basal, HER2-enriched)...
August 10, 2017: Current Oncology Reports
https://www.readbyqxmd.com/read/28779846/immune-modulation-by-a-cellular-network-of-mesenchymal-stem-cells-and-breast-cancer-cell-subsets-implication-for-cancer-therapy
#8
Hussam S Eltoukhy, Garima Sinha, Caitlyn A Moore, Oleta A Sandiford, Pranela Rameshwar
The immune modulatory properties of mesenchymal stem cells (MSCs) are mostly controlled by the particular microenvironment. Cancer stem cells (CSCs), which can initiate a clinical tumor, have been the subject of intense research. This review article discusses investigative studies of the roles of MSCs on cancer biology including on CSCs, and the potential as drug delivery to tumors. An understanding of how MSCs behave in the tumor microenvironment to facilitate the survival of tumor cells would be crucial to identify drug targets...
August 1, 2017: Cellular Immunology
https://www.readbyqxmd.com/read/28770278/an-unbiased-in-vivo-functional-genomics-screening-approach-in-mice-identifies-novel-tumor-cell-based-regulators-of-immune-rejection
#9
Casey W Shuptrine, Reham Ajina, Elana J Fertig, Sandra A Jablonski, H Kim Lyerly, Zachary C Hartman, Louis M Weiner
The clinical successes of immune checkpoint therapies for cancer make it important to identify mechanisms of resistance to anti-tumor immune responses. Numerous resistance mechanisms have been identified employing studies of single genes or pathways, thereby parsing the tumor microenvironment complexity into tractable pieces. However, this limits the potential for novel gene discovery to in vivo immune attack. To address this challenge, we developed an unbiased in vivo genome-wide RNAi screening platform that leverages host immune selection in strains of immune-competent and immunodeficient mice to select for tumor cell-based genes that regulate in vivo sensitivity to immune attack...
August 2, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28756536/therapeutic-blockade-of-foxp3-in-experimental-breast-cancer-models
#10
Mariela A Moreno Ayala, María Florencia Gottardo, Mercedes Imsen, Antonela S Asad, Elisa Bal de Kier Joffé, Noelia Casares, Juan José Lasarte, Adriana Seilicovich, Marianela Candolfi
PURPOSE: Regulatory T cells (Tregs) impair the clinical benefit of cancer immunotherapy. To optimize the antitumor efficacy of therapeutic dendritic cell (DC) vaccines, we aimed to inhibit Foxp3, a transcription factor required for Treg function. METHODS: Mice bearing established syngeneic LM3 and 4T1 breast tumors were treated with antitumor DC vaccines and a synthetic peptide (P60) that has been shown to inhibit Foxp3. RESULTS: Treatment with P60 improved the therapeutic efficacy of DC vaccines in these experimental models...
July 29, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28750120/association-between-genomic-metrics-and-immune-infiltration-in-triple-negative-breast-cancer
#11
Thomas Karn, Tingting Jiang, Christos Hatzis, Nicole Sänger, Ahmed El-Balat, Achim Rody, Uwe Holtrich, Sven Becker, Giampaolo Bianchini, Lajos Pusztai
Importance: Why some triple-negative breast cancers (TNBCs) have high and others have low immune cell infiltration is unknown. Understanding how immune surveillance shapes the cancer genome could help in the selection of patients and the development of more effective immunotherapy strategies. Objective: To examine the association between genomic metrics and the extent of immune infiltration in TNBCs. Design, Setting, and Participants: This study, performed from June 1, 2015, through January 31, 2017, used DNA and RNA sequencing data and messenger RNA expression results from The Cancer Genome Atlas (TCGA) breast cancer data set (n = 1215) to calculate previously described immune metagene expression values and histologic lymphocyte counts to quantify immune infiltration and assign prognostic categories to TNBCs...
July 27, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/28749856/evaluation-of-prognostic-factors-and-proposed-changes-to-the-modified-tokuhashi-score-in-patients-with-spinal-metastases-from-breast-cancer
#12
Kimberly-Anne Tan, Jiong Hao Tan, Aye Sandar Zaw, Joel Yong Hao Tan, Hwee Weng Dennis Hey, Naresh Kumar
STUDY DESIGN: A retrospective study of all patients with histologically-confirmed breast cancer spinal metastases presenting to a single instituition between May 2001-April 2012. OBJECTIVES: To investigate if the 2014mT is more accurate than the 2005mT. SUMMARY OF BACKGROUND DATA: The commonly used 2005 modified Tokuhashi score (2005mT) has become more inaccurate as oncologists move towards treating tumours according to their molecular and genomic profile, rather than their tissue-of-origin...
July 26, 2017: Spine
https://www.readbyqxmd.com/read/28749113/increased-tumour-infiltration-of-cd4-and-cd8-t-lymphocytes-in-patients-with-triple-negative-breast-cancer-suggests-susceptibility-to-immune-therapy
#13
Bushra Sikandar, Muhammad Asif Qureshi, Saima Naseem, Saeed Khan, Talat Mirza
Background: Patients with triple negative breast cancer (TNBC) have limited therapeutic options, largely because the complex tumour environment is not well-characterized. These patients are potential, but largely un-fathomed, candidates for immunotherapy. It is therefore highly relevant to characterize leukocyte complexity in TNBCs. Objective: To investigate leukocyte complexity in tumour environment of patients with TNBCs. Materials and methods: A total of 104 consecutive breast cancer patients undergoing mastectomy were recruited in the study after ethical approval...
July 27, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/28735814/tyrosine-kinase-inhibitors-as-modulators-of-trastuzumab-mediated-antibody-dependent-cell-mediated-cytotoxicity-in-breast-cancer-cell-lines
#14
Denis M Collins, Kathy Gately, Clare Hughes, Connla Edwards, Anthony Davies, Stephen F Madden, Kenneth J O'Byrne, Norma O'Donovan, John Crown
BACKGROUND: Trastuzumab is an anti-HER2 monoclonal antibody (mAb) therapy capable of antibody-dependent cell-mediated cytotoxicity (ADCC) and used in the treatment of HER2+ breast cancer. Through interactions with FcƴR+ immune cell subsets, trastuzumab functions as a passive immunotherapy. The EGFR/HER2-targeting tyrosine kinase inhibitor (TKI) lapatinib and the next generation TKIs afatinib and neratinib, can alter HER2 levels, potentially modulating the ADCC response to trastuzumab...
July 15, 2017: Cellular Immunology
https://www.readbyqxmd.com/read/28735162/tumor-infiltrating-lymphocytes-in-breast-cancer-according-to-tumor-subtype-current-state-of-the-art
#15
REVIEW
Cinzia Solinas, Luisa Carbognin, Pushpamali De Silva, Carmen Criscitiello, Matteo Lambertini
The recent success of the immune checkpoint blockade in cancer immunotherapy has modified the treatment algorithms in a variety of aggressive neoplastic diseases. Nevertheless, optimal selection of ideal candidates to these drugs remains a challenge. The presence, location and composition of a pre-existing tumor immune infiltrate seem to impact on the benefit from these treatments. The association between the presence of baseline tumor-infiltrating lymphocytes (TIL) and patients' outcomes has been widely investigated in breast cancer, although immunotherapeutic strategies have historically been less successful with respect to other neoplastic diseases such as melanoma and kidney cancer...
July 20, 2017: Breast: Official Journal of the European Society of Mastology
https://www.readbyqxmd.com/read/28733529/immunotherapy-of-wap-tnp-mice-with-early-stage-mammary-gland-tumors
#16
Michael Bruns, Wolfgang Deppert
The SV40 transgenic BALB/c mouse based WAP-T/WAP-TNP model for triple-negative breast cancer allows the analysis of parameters influencing immunotherapeutic approaches. Except for WAP-TNP tumors expressing the immune-dominant LCMV NP-epitope within SV40 T-antigen (T-AgNP) which is not expressed by T-Ag of WAP-T tumors, the tumors are extremely similar. Comparative anti-PD1/PD-L1 immunotherapy of WAP-T and WAP-TNP mice supported the hypothesis that the immunogenicity of tumor antigen T-cell epitopes strongly influences the success of immune checkpoint blockade therapy, with highly immunogenic T-cell epitopes favoring rapid CTL exhaustion...
June 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28731046/pd-l1-expression-and-the-immune-microenvironment-in-primary-invasive-lobular-carcinomas-of-the-breast
#17
Elizabeth D Thompson, Janis M Taube, Rebecca J Asch-Kendrick, Aleksandra Ogurtsova, Haiying Xu, Rajni Sharma, Alan Meeker, Pedram Argani, Leisha A Emens, Ashley Cimino-Mathews
Tumor-infiltrating lymphocytes and immune checkpoint proteins such as PD-L1 are potential prognostic factors and therapeutic targets in breast cancer. Most studies characterizing the breast tumor immune microenvironment have focused on ductal carcinomas. Here we investigate the tumor microenvironment of primary invasive lobular carcinomas. Previously constructed tissue microarrays of 47 lobular carcinomas were labeled by immunohistochemistry for PD-L1, CD8, CD20, and FoxP3. The stromal immune infiltrate density was qualitatively scored as a percentage of tumor area: 1+ (<5%); 2+ (5-10%); 3+ (10-15%); or 4+ (>50%)...
July 21, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28729550/anti-tumor-activity-and-immunotherapeutic-potential-of-a-bisphosphonate-prodrug
#18
Yoshimasa Tanaka, Masashi Iwasaki, Kaoru Murata-Hirai, Kenji Matsumoto, Kosuke Hayashi, Haruki Okamura, Tomoharu Sugie, Nagahiro Minato, Craig T Morita, Masakazu Toi
Bisphosphonates have benefits in breast cancer and multiple myeloma patients and have been used with adoptive immunotherapy with γδ T cells expressing Vγ2 Vδ2 TCRs. Although treatment with γδ T cells is safe, it has shown limited efficacy. Present bisphosphonates stimulate γδ T cells but were designed to inhibit bone resorption rather than treating cancer and have limited oral absorption, tumor cell entry, and cause bone side effects. The development of phosphate and phosphonate nucleotide prodrugs has led to important drugs for hepatitis C and HIV...
July 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28728493/treating-breast-cancer-with-cell-based-approaches-an-overview
#19
Susanna Gallo, Dario Sangiolo, Fabrizio Carnevale Schianca, Massimo Aglietta, Filippo Montemurro
Breast cancer is the most common malignancy in women. Despite there being considerable progress in the treatment of this disease, metastatic dissemination is still considered an incurable condition at the present time, causing 500,000 deaths worldwide every year. Although most of the research efforts have been focused on pharmacological approaches, over the last three decades, the use of bone marrow and peripheral blood-derived cell therapy approaches have been attempted and developed. Areas covered: This review will briefly address cell therapy for breast cancer, including autologous stem cell transplantations for overcoming the myelosuppressive effects of high-dose chemotherapy, allogeneic stem cell transplants and adoptive immunotherapy using bone-marrow derived T-cells...
July 20, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28718331/entinostat-for-the-treatment-of-breast-cancer
#20
REVIEW
Dario Trapani, Angela Esposito, Carmen Criscitiello, Luca Mazzarella, Marzia Locatelli, Ida Minchella, Saverio Minucci, Giuseppe Curigliano
Breast cancer accounts for 29% of malignant tumors. It is an heterogenous disease covering a spectrum of different molecular subtypes. Epigenetic aberrations may affect gene expression through DNA and histone proteins modifications thus promoting tumor progression and resistance to anti- tumor treatment. Area covered: This article explores the potential role of entinostat in the treatment of breast cancer. The clinical trials evaluating entinostat are discussed, highlighting preclinical data and early-phase clinical studies results...
August 2017: Expert Opinion on Investigational Drugs
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